Common bile duct stone (CBDS) recurrence remains a clinical concern after endoscopic stone clearance. Although both endoscopic sphincterotomy (EST) and endoscopic papillary balloon dilation (EPBD) are widely used, whether differences in papillary sphincter disruption influence long-term recurrence and pneumobilia remains uncertain. To compare long-term CBDS recurrence after EPBD versus EST and to explore the associations among sphincterotomy extent, pneumobilia, and recurrence. Adults with native papillae who underwent ERCP for CBDSs ≤10 mm at two centers from 2004 to 2024 were retrospectively analyzed. Patients treated with EST or EPBD alone who achieved complete stone clearance were included. The primary outcome was CBDS recurrence. Inverse probability of treatment weighting (IPTW), Cox regression, and propensity-score matching were used to adjust for confounding. Among 4,848 screened, 1,119 were included (971 EST and 148 EPBD). Recurrence occurred in 151 EST patients (15.6
Slow-transit constipation (STC) is a subtype of chronic constipation characterized by delayed colonic transit without obstructive defecation. Because in vivo human experimentation is constrained, animal models remain the primary tool for probing STC pathogenesis and testing therapies, yet no unified framework exists for judging howwell current models reproduce human disease. This review systematically appraises the reported STC animal models against a single validity framework and identifies design criteria for the next generation of models. We reviewed pharmacological agent-induced models (loperamide, diphenoxylate, alosetron, morphine, atropine), a physical stimulus model (ice-water gavage), surgical models (rectal distension, partial outlet obstruction, chemical ablation of the enteric plexus), and a naturally occurring inbred strain (the CFP/Yit mouse), and appraised each using the Face–Construct–Predictive validity framework. Existing models show substantial gaps in face validity (drug-withdrawal-dependent, self-limiting constipation rather than chronic progressive dysmotility), construct validity (few reproduce enteric glial cell loss, enteric neuronde generation, interstitial cell of Cajal depletion, and inflammatory infiltration), and predictive validity (induction agents confound therapeutic readouts). Advances in enteric glial biology, microbiota–short-chain fatty acid–motility signalling, single-cell transcriptomics of enteric glia, and genetic susceptibility point toward transgenic, pelvic-nerve-intervention, selective enteric glial ablation, and organoid–enteric nervous system co-culture designs, with sex-stratified evaluation and systematic clinical translation studies. The Face–Construct–Predictive framework exposes the translational shortfall of current STC animal models and defines concrete design criteria for clinically relevant successors, guiding model selection and prioritizing future research.
To critically examine the evidence for and against reversibility of gastric intestinal metaplasia (GIM) after Helicobacter pylori eradication, reframe the two-decade controversy, and propose a hypothesis-generating framework for risk-stratified management. Narrative synthesis of meta-analyses, cohort studies, randomized controlled trials, and mechanistic studies (2007–2026) identified through PubMed and Web of Science. The evidence has swung from early meta-analyses (2007–2011) concluding against IM reversibility to recent syntheses (2023–2025) demonstrating regression with prolonged follow-up. In early 2026, two reviews reached opposing conclusions: Song and Yu proposed an oncogenic memory model of persistent mucosal injury, epigenetic and immune alterations, and microbiome dysbiosis, while Chen et al. maintained that part of GIM exhibits meaningful reversibility. Extending this framework, we propose a fourth, largely irreversible dimension—histological memory—encompassing spasmolytic polypeptide-expressing metaplasia (SPEM) progression and stem cell niche alteration, which deepens the mucosal injury component of oncogenic memory. Known predictive factors (OLGA/OLGIM stage, subtype, age, eradication timing, and oncogenic memory burden) are organized into a unified reversibility gradient that reframes the binary question in risk-stratified terms, from which a hypothesis-generating three-tier surveillance framework is derived. GIM reversibility is a continuous function of lesion characteristics, host factors, time since eradication, intervention intensity, and oncogenic memory burden rather than a binary property. The clinically relevant question is whose GIM, under what conditions, over what time frame, and with what residual risk reduction. The frameworks are hypothesis-generating, not validated clinical recommendations; prospective validation of risk-stratified surveillance represents the most urgent research priority.
Tenapanor is approved for the treatment of irritable bowel syndrome with constipation (IBS-C) in adults. The impact of prior IBS-C prescription treatment(s) on the therapeutic efficacy of tenapanor is unknown. To assess whether prior IBS-C prescription medication use affected clinical response to tenapanor in pooled data from the phase 3 T3MPO-1 and T3MPO-2 trials. Adults with IBS-C were randomized to twice-daily tenapanor or placebo for 12 (T3MPO-1) or 26 (T3MPO-2) weeks. Patients discontinued use of prior IBS-C prescription medications, which were prohibited per protocol, during screening. Post-hoc analyses evaluated responder rates over the first 12 weeks in patients with and without prior IBS-C prescription medication use. The primary composite responder endpoint was defined as achieving ≥ 1 increase in weekly complete spontaneous bowel movements and ≥ 30
Severe acute pancreatitis (SAP) is often accompanied by intestinal mucosal barrier injury (IBI), in which ferroptosis of intestinal epithelial cells plays a critical role. The cellular zinc transporter ZIP7 has been reported to be closely associated with ferroptosis. This study aimed to investigate the regulatory role of zinc transporter ZIP7 on ferroptosis and its underlying mechanism in SAP-induced IBI. Sodium taurocholate (5
